Deep Brain Stimulation (DBS) for the Management of Treatment Refractory Negative Symptoms in Schizophrenia

Center for Addiction and Mental Health (CAMH)

Status and phase

Withdrawn

Phase 1

Conditions

Schizophrenia; Negative Type

Treatments

Procedure: Deep Brain Stimulation

Study type

Interventional

Funder types

Other

Identifiers

NCT01725334

078/2011

Details and patient eligibility

About

Schizophrenia is a complex, challenging, and heterogeneous psychiatric condition, affecting up to 0.5% of the population and responsible for nearly 2% of all Canadian health-care expenditure. Much of the morbidity of the illness is related to its negative symptoms, including amotivation, asociality, anhedonia and flattened emotional affect, which lead to functional impairment and withdrawal from social and occupational domains. In contrast to positive symptoms, such as hallucinations and delusions, there are currently no effective treatments for negative symptoms, which experts recognize are largely responsible for the long-term disability of a majority of patients with schizophrenia. Advances in neuroscience have allowed a greater understanding of negative symptoms and have identified key structures and circuits believed to generate and maintain them. Here, we propose the application of a targeted therapy, deep brain stimulation, to alter the circuits driving negative symptoms.

Full description

Schizophrenia is a public health challenge with a large proportion of patients suffering from predominantly negative symptoms and who derive no benefit from currently available treatments. Advances in neuroscience have allowed a greater understanding of negative symptoms and have identified key structures and circuits believed to generate and maintain them. Here, we propose the application of a targeted therapy, deep brain stimulation (DBS), to alter the circuits driving negative symptoms. This is a phase I, non-blinded, non-randomized, pilot trial, exploring the safety and efficacy of DBS in patients with refractory negative symptoms of schizophrenia. Patients must be identified and approached by their treating psychiatrist regarding this study. Patients will be given several opportunities to review the study details with the investigators before the informed consent is presented. All eligible patients will also be reviewed by an independent non-study affiliated psychiatrist for confirmation of their diagnosis and assessment of study eligibility. The total study duration will be one year for each patient, who will undergo regular imaging and psychiatric analyses.

Sex

All

Ages

25 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or Female patients between the age of 25-65
DSM IV-TR diagnosis of Schizophrenia Predominant Negative Subtype, as determined by the SANS and the Schedule for the Deficit Syndrome (SDS)
Greater negative than positive scores on the Positive and Negative Symptoms of Schizophrenia Scale (PANSS)
Confirmation of diagnosis by independent, non-study affiliated psychiatrist
Disease duration of > 5 years
Failure of medical therapy, defined as follows:
Failure of a minimum of three anti-psychotic treatments for specifically negative symptoms of schizophrenia (including clozapine)
No underlying neurological disease - No other active Axis I or Axis II co-morbidity that is the focus of clinical attention
Able to give informed consent: i)Deemed competent by two independent psychiatrists (one study psychiatrist and one non-study psychiatrist); ii) Score of > 70 on MacCat-CR
Able to comply with all testing and follow-up visit requirements defined by the Study Protocol
Mini mental status examination (MMSE)score > 25
Pre-menopausal women must agree to use acceptable methods of birth control (radiation risk of PET)

Exclusion criteria

Alcohol or substance dependence or abuse within 6 months, excluding nicotine or caffeine.
Current suicidal ideation, plan or intent for self-harm.
A suicide attempt in the past 1 year
Diagnosis of Major Depressive Disorder or Bipolar Depression
Major medical illness, cardiac pacemaker/defibrillator, and other implanted stimulator
Likely to relocate or move to a location distant from the study site within one year of enrollment
Any contraindication to MRI or PET scanning
Inability to provide consent, as well as an inability to appreciate the details and risk of the trial's procedures; competence will be assessed by two independent psychiatrists (one study psychiatrist, and one non-study psychiatrist)